Virtual screening and biological evaluation of novel small molecular inhibitors against protein arginine methyltransferase 1 (PRMT1)
文献类型：期刊论文
| 作者 | Xie, Yiqian2,3; Zhou, Ran3; Lian, Fulin3; Liu, Yan3; Chen, Limin3; Shi, Zhe1; Zhang, Naixia3 ; Zheng, Mingyue3; Shen, Bairong2; Jiang, Hualiang3
|
| 刊名 | ORGANIC & BIOMOLECULAR CHEMISTRY
 |
| 出版日期 | 2014 |
| 卷号 | 12期号:47页码:9665-9673 |
| ISSN号 | 1477-0520 |
| DOI | 10.1039/c4ob01591f |
| 文献子类 | Article |
| 英文摘要 | Protein arginine methylation is a common post-translational modification which is crucial for a variety of biological processes. Dysregulation of protein arginine methyltransferases (PRMTs) activity has been implicated in cancer and other serious diseases. Thus, small molecule inhibitors against PRMT have great potential for therapeutic development. Herein, through the combination of virtual screening and bio-assays, six small molecular compounds were identified as PRMT1 inhibitors. Amongst them, the binding affinity of compounds DCLX069 and DCLX078 with PRMT1 was further validated by T1 rho and saturation transfer difference (STD) NMR experiments. Most important of all, both compounds effectively blocked cell proliferation in breast cancer, liver cancer and acute myeloid leukemia cell lines. The binding mode analysis from molecular docking simulations theoretically indicated that both inhibitors occupied the SAM binding pocket to exert the inhibitory effect. Taken together, our compounds enriched the structural scaffolds as PRMT1 inhibitors and afforded clues for further optimization. |
| WOS关键词 | ADENOSYL-L-METHIONINE ; TRANSCRIPTIONAL ACTIVATION ; IN-VIVO ; METHYLATION ; DOCKING ; BINDING ; GENE ; SPECIFICITY ; INTERACTS ; SURAMIN |
| 资助项目 | Hi-Tech Research and Development Program of China[2012AA020302] ; National Natural Science Foundation of China[21210003] ; National Natural Science Foundation of China[81302700] ; National Natural Science Foundation of China[81230076] ; National Natural Science Foundation of China[21272246] ; China Postdoctoral Science Foundation[7131701713] ; Natural Science Foundation of the Jiangsu Higher Education Institutions[13KJB520022] ; Chinese Academy of Sciences (100 Talents Program)[00000000] ; National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program"[2014ZX09507002] |
| WOS研究方向 | Chemistry |
| 语种 | 英语 |
| WOS记录号 | WOS:000345066100022 |
| 出版者 | ROYAL SOC CHEMISTRY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/277259]  |
| 专题 | 药物发现与设计中心 中科院受体结构与功能重点实验室 新药研究国家重点实验室 分析化学研究室 战略规划处 |
| 通讯作者 | Liang, Zhongjie |
| 作者单位 | 1.Shanghai ChemPartner LifeSci Co Ltd, In Vitro Biol, Shanghai 201203, Peoples R China 2.Soochow Univ, Ctr Syst Biol, Suzhou 215006, Jiangsu, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Xie, Yiqian,Zhou, Ran,Lian, Fulin,et al. Virtual screening and biological evaluation of novel small molecular inhibitors against protein arginine methyltransferase 1 (PRMT1)[J]. ORGANIC & BIOMOLECULAR CHEMISTRY,2014,12(47):9665-9673. |
| APA | Xie, Yiqian.,Zhou, Ran.,Lian, Fulin.,Liu, Yan.,Chen, Limin.,...&Luo, Cheng.(2014).Virtual screening and biological evaluation of novel small molecular inhibitors against protein arginine methyltransferase 1 (PRMT1).ORGANIC & BIOMOLECULAR CHEMISTRY,12(47),9665-9673. |
| MLA | Xie, Yiqian,et al."Virtual screening and biological evaluation of novel small molecular inhibitors against protein arginine methyltransferase 1 (PRMT1)".ORGANIC & BIOMOLECULAR CHEMISTRY 12.47(2014):9665-9673. |
入库方式： OAI收割
来源：上海药物研究所
浏览0
下载0
收藏0
其他版本
除非特别说明，本系统中所有内容都受版权保护，并保留所有权利。